PB2153: IMPACT OF EXTRAMEDULLARY DISEASE IN PATIENTS WITH MULTIPLE MYELOMA: MULTICENTER RETROSPECTIVE ANALYSIS
Authors: Rita Costa e Sousa, João Gaião Santos, Pedro Jorge Pinto, Adriana Roque, Marília Gomes, Henrique Coelho, Catarina Geraldes
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Extramedullary disease (EMD) is a rare form of multiple myeloma (MM), with an incidence that ranges from 0.5-4.8% in patients (pts) with newly diagnosed MM and 3.4-14% in relapsed/refractory MM. Generally, it presents as an aggressive form of MM and is characterized by high-risk genetic features, resistance to therapies and poor prognosis, compared with bone marrow-restricted disease. Aims: To characterize pts with MM and EMD and assess the impact of EMD on survival. Methods: Multicenter, retrospective analysis of pts diagnosed with MM and EMD between 2007 and 2022. Statistical analysis was performed using SPSS statistics v26. Kaplan-Meier method was used to assess the progression-free survival (PFS) and overall survival (OS), and the log-rank test was used to analyze prognostic variables. Results: We included 33 pts with a median age at diagnosis of 67 years (42-84) and 57.6% were male. The M-component was IgG in 54.5%, IgA in 27.3%, light-chain in 12.1% and IgD in 6.1%. Among the 30 pts with available data, 12 (36.4%) were ISS III. Cytogenetics was available in 23 pts, of which 9 had high-risk abnormalities: amp(1q) n=3, del(17p) n=4, del(17p)+amp(1q) n=1 and del(17p)+t(14,14)+t(14,16) n=1. Fourteen pts (42.4%) presented with EMD at diagnosis of MM (group A) and the most frequent EMD locations were lymph nodes (28.4%) and liver (14.3%). Nineteen pts (57.6%) presented EMD at relapse (group B) after a median time of 38 month after diagnosis (6-125), 73.6% of whom after 3 lines of therapy and the most frequent EMD location were lymph nodes (26.0%). One patient died prior to induction therapy and 1 patient had surgical excision of a localized EMD. Regarding 1st line therapy, 26 pts (78.8%) were treated with bortezomib-based regimens (VRD, VTD, VCD, VMP, VD), 2 (6.0%) with MPT, 1 (3.0%) with DRD, 1 (3.0%) with VBMCP/VBAD and 1 (3.0%) with idarrubicin-dexamethasone. In terms of response to 1st line therapy, 9 pts (64.3%) from group A had available response and 44.4% obtained CR, 44.4% VGPR and 11.1% were primary refractory. Eight pts in group A (57%) started 1st line therapy with bortezomib-based regimens, 87.5% of which achieved VGPR or better. As for group B, from 17 (89.5%) evaluable pts, 26.3% obtained CR, 36.8% VGPR, 21.1% PR and 5.3% showed PD. After a median follow-up of 36 months since the diagnosis of MM, 23 pts (69.7%) relapsed, of which 8 (34.8%) started 2nd line therapy with daratumumab-based regimens, 5 (21.7%) with bortezomib-based regimens (VRD, VCD, VMP, VD), 5 (21.7%) with RD, 2 (8.7%) with KRD, 1 (4.3%) with TCD, 1 (4.3%) with MP and 1 (4.3%) with D-PACE. Median PFS after the diagnosis of EMD was 6 months, with no differences between groups A and B (7 vs. 5 months; p=0.698; HR=0.855; 95%CI (0.389-1.880)). Median OS after the diagnosis of EMD was 14 months, with significant differences between groups A and B (29 vs. 9 months; p<0.05; HR=0.294; 95%CI (0.113-0.769)). Summary/Conclusion: In conclusion, our results support the available literature data, confirming the poor prognosis of EMD in patients with MM. However, it’s worth mentioning that some patients included were diagnosed more than 15 years ago, at a time when effective therapies were limited. Nonetheless, the lack of effective therapeutic options able to induce prolonged PFS and OS makes the management of these patients very challenging. The best approach of patients with EMD is still an unmet need. Keywords: Multiple myeloma